Overcoming Immunogenicity to Anti-TNF Therapy by Reactively Adding an Immunomodulator

Excerpt

Anti-tumor necrosis factor (TNF) therapy with the monoclonal antibodies infliximab and adalimumab remains a key pillar in the expanding therapeutic armamentarium in the management of inflammatory bowel disease [1]. This class of advanced therapy is not only highly efficacious in moderate-to-severe Crohn’s disease (CD) and ulcerative colitis (UC), but also the first choice in perianal CD and as rescue therapy in acute severe UC [2, 3]. Unfortunately, immunogenic failure, due to the development of anti-drug antibodies, is frequently observed, occurring in up to 65.3% of patients treated with infliximab and up to 38% of those treated with adalimumab [4]. Once present, anti-drug antibodies can increase drug clearance while diminishing response, or can produce adverse effects. Though concomitant immunomodulation with thiopurines or methotrexate reduces the risk of immunogenic failure and improves durability of response, it is associated with potentially serious adverse effects including opportunistic infection and lymphoma. Immunogenic loss of response often leads to a change in therapy out-of-class, or, where appropriate, change within class to an alternate anti-TNF, in which subsequent immunogenicity can be mitigated with the use of concomitant immunomodulation [5]. Accordingly, strategies to manage immunogenicity can be broadly divided into prevention (proactive) or to management once recognized (reactive). …